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1.
Vaccine ; 38(27): 4316-4324, 2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-32387009

RESUMO

BACKGROUND: Emerging observational evidence suggests a single-dose of human papillomavirus (HPV) vaccine may be protective against vaccine-targeted HPV infection and associated cervical dysplasia. We aimed to demonstrate whether a single dose of quadrivalent HPV (4vHPV) vaccine was immunogenic and reduced HPV detection rates in young women in Mongolia. We also assessed knowledge and attitudes regarding HPV and the HPV vaccine. METHODS: A retrospective paired cohort study was undertaken to evaluate the effect of a single dose of 4vHPV, given at age 11-17 years in 2012, on HPV detection rates, when compared with unvaccinated women. Real time PCR was performed on self-administered vaginal swabs for HPV detection. An immunological analysis detecting neutralising antibodies (NAb) to high-risk HPV (HRHPV) genotypes 16 and 18 was performed on sera from a subset of 58 participants. Questionnaires evaluated knowledge, attitudes and self-swab acceptability. FINDINGS: A total of 475 women (mean age 20.4 years ± 1.6) were recruited; 118 vaccinated and 357 unvaccinated women. The prevalence of vaccine-targeted HRHPV16 and 18 was reduced by 92% (95%CI 44-99%) in the vaccinated (1·1%) compared with the unvaccinated (15.4%) group. The percentage of non-vaccine HPV genotypes was similar between vaccinated (26.5%) and unvaccinated (26.7%) groups. Approximately 90% and 58% of vaccinated women remained seropositive after six years for HRHPV16 and 18, respectively, with neutralising antibody levels 5- and 2-fold higher than unvaccinated women (p < 0.001). INTERPRETATION: One dose of 4vHPV vaccine reduces vaccine-targeted HPV genotypes, six years following vaccination, with high levels of HR genotype seropositivity among young Mongolian women.

2.
Clin Infect Dis ; 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32342984

RESUMO

BACKGROUND: Gay and bisexual men (GBM) are disproportionately affected by anal cancer. Prevention is hindered by incomplete understanding of the natural history of its precursor, anal high-grade squamous intraepithelial lesions (HSIL). METHODS: The Study of the Prevention of Anal Cancer, conducted between 2010 and 2018, enrolled human immunodeficiency virus (HIV)-positive and HIV-negative GBM aged ≥35 years. Anal cytology and high-resolution anoscopy (HRA) were performed at baseline and 3 annual visits. A composite HSIL diagnosis (cytology ± histology) was used. Cytological high-grade squamous intraepithelial lesions (cHSIL) incidence and clearance rates were calculated with 95% confidence intervals (CIs). Predictors were calculated using Cox regression with hazard ratios (HRs) and 95% CIs. RESULTS: Among 617 men, 220 (35.7%) were HIV-positive, median age 49 years. And 124 incident cHSIL cases occurred over 1097.3 person-years (PY) follow-up (11.3, 95% CI 9.5-13.5 per 100 PY). Significant bivariate predictors of higher incidence included age <45 years (HR 1.64, 95% CI 1.11-2.41), HIV positivity (HR 1.43, 95% CI .99-2.06), prior SIL diagnosis (P-trend < .001) and human papillomavirus (HPV)16 (HR 3.39, 2.38-4.84). Over 695.3 PY follow-up, 153 HSIL cleared (clearance 22.0, 95% CI 18.8-25.8 per 100 PY). Predictors were age < 45 years (HR 1.52, 1.08-2.16), anal intraepithelial neoplasia (AIN)2 rather than AIN3 (HR 1.79, 1.29-2.49), smaller lesions (HR 1.62, 1.11-2.36) and no persistent HPV16 (HR 1.72, 1.23-2.41). There was 1 progression to cancer (incidence 0.224, 95% CI .006-1.25 per 100 PY). CONCLUSION: These data strongly suggest that not all anal HSIL detected in screening requires treatment. Men with persistent HPV16 were less likely to clear HSIL and are more likely to benefit from effective HSIL treatments.

4.
J Infect Dis ; 221(6): 1017-1024, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32031634

RESUMO

BACKGROUND: The basis of fluoroquinolone treatment failure for Mycoplasma genitalium is poorly understood. METHODS: To identify mutations associated with failure we sequenced key regions of the M. genitalium parC and gyrA genes for patients undergoing sequential therapy with doxycycline-moxifloxacin (201 patients, including 21 with failure) or doxycycline-sitafloxacin (126 patients, including 13 with failure). RESULTS: The parC G248T/S83I mutation was more common among patients with failed sequential doxycycline-moxifloxacin (present in 76.2% of failures vs 7.8% cures, P < .001) or doxycycline-sitafloxacin (50% vs 16.8%, respectively; P = .01) treatment. Doxycycline-sitafloxacin was more efficacious than doxycycline-moxifloxacin against infections carrying the parC mutation conferring S83I amino acid change. Treatment was more likely to fail in these infections if they had a concurrent gyrA mutation (M95I or D99N) (P = .07 for doxycycline-moxifloxacin group and P = .009 for doxycycline-sitafloxacin group), suggesting an additive effect. CONCLUSIONS: This study indicates that parC G248T/S83I mutations contribute to failure of moxifloxacin and sitafloxacin, and the findings will inform the development of quinolone resistance assays needed to ensure optimal selection of antimicrobials for M. genitalium.

5.
Acad Pediatr ; 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31987891

RESUMO

OBJECTIVE: Facebook is a popular social media platform used globally to keep connected and informed. The aims of this study were to determine the contribution of Facebook to the participation rate of young adults enrolled in a longitudinal cohort study, and to examine systematic differences in participants recruited through Facebook compared with those recruited through traditional methods. METHODS: Potential participants comprised 297 consecutive survivors born extremely preterm (<28 weeks' gestation) or extremely low birth weight (<1000 g birth weight) in 1991-92 in the state of Victoria, Australia, and 260 contemporaneously recruited normal birth weight (>2499 g birth weight) controls who had participated previously in a prospective cohort study. At 25 years of age participants were approached initially via traditional methods (mail, telephone, texts), and subsequently by Facebook for those difficult to contact or locate. RESULTS: Contact was attempted with 523 young adults via traditional methods and 49% (n = 255) agreed to participate. Of the 208 participants unable to be located or contacted via traditional methods, 153 were subsequently located via Facebook. Of these 82% (n = 125) responded promptly within a day of receiving the Facebook invite, and 41% (n = 63) ultimately participated. The participation rate increased from 49% (255 of 523) to 61% (318 of 523) with the addition of Facebook, an absolute increase of 12%. Participants recruited by Facebook were slightly older, had lower rates of school completion and lower cognitive score at 18 years of age compared with those recruited via traditional methods. CONCLUSIONS: Using Facebook improved participation of young adults enrolled in this longitudinal preterm follow up study, 25 years after original recruitment.

6.
J Med Microbiol ; 69(2): 244-248, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31958047

RESUMO

Introduction. Mycoplasma genitalium is a sexually transmitted organism with high levels of resistance to the recommended first-line therapy, azithromycin. The ResistancePlus MG test concurrently detects M. genitalium, and the presence of macrolide-resistance mutations (MRM). European, UK and Australian guidelines recommend a diagnostic test that reports MRM to optimize treatment through resistance-guided therapy. Hence, for samples collected for use on other platforms, reflex testing using the ResistancePlus MG test would be beneficial.Aim. To validate the ResistancePlus MG assay using samples collected in Aptima buffer for testing on the Hologic Panther.Methodology. Positive (n=99) and negative (n=229) clinical samples collected in Aptima buffer were extracted on the MagNA Pure 96 (Roche Diagnostics), and tested with the ResistancePlus MG test on the LightCycler 480 II (Roche Diagnostics). Results were compared to matched samples collected using standard sample collection (urine or swab resuspended in PBS), with positive percent agreement (PPA), negative percent agreement (NPA) and Cohen's Kappa statistic.Results. The ResistancePlus MG test had high performance with a 200 µl input volume (PPA/NPA for M. genitalium detection, 92.9 % [95 % confidence interval (CI): 85.5-96.9]/100 % [95 % CI: 97.9-100], MRM detection, 96.9 % [95 % CI: 88.2-99.5]/85.7 % [95 % CI: 66.4-95.3]) and for 1 ml input volume (PPA/NPA for M. genitalium detection, 95.9%/96.6%, MRM detection, 98.4%/90.3%). Samples remained positive after storage at room temperature beyond the manufacturer-recommended storage of <60 days (mean storage time for 1 ml extraction: 129 days).Conclusion. Samples collected using Aptima collection kits are suitable for reflex testing using the ResistancePlus MG test, allowing detection of macrolide resistance.


Assuntos
Antibacterianos/farmacologia , Testes Diagnósticos de Rotina/métodos , Farmacorresistência Bacteriana , Infecções por Mycoplasma/microbiologia , Mycoplasma genitalium/efeitos dos fármacos , Mycoplasma genitalium/isolamento & purificação , Austrália , Testes Diagnósticos de Rotina/instrumentação , Humanos , Macrolídeos/farmacologia , Infecções por Mycoplasma/diagnóstico , Mycoplasma genitalium/genética , Kit de Reagentes para Diagnóstico , Manejo de Espécimes
7.
Allergy ; 75(1): 127-136, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31608448

RESUMO

BACKGROUND: Probiotic supplementation to mothers and/or their term-born infants has been suggested to prevent allergic disease, in particular eczema; however, no studies have investigated probiotics for prevention of allergic diseases in very preterm infants. We evaluated the effect of a postnatal probiotic combination on development of allergic diseases in very preterm infants. METHODS: This sub-study was an a priori secondary outcome of the ProPrems multi-center, double-blind, placebo-controlled randomized trial (ANZCTR:12607000144415). ProPrems randomized 1099 very preterm infants to receive a probiotic combination or placebo from soon after birth until discharge from hospital or term corrected age (CA), whichever was earlier. Allergic disease (eczema, atopic eczema, food allergy, wheeze, atopic sensitization) was assessed in a subgroup of ProPrems infants (n = 281) as close to 12 months CA as possible by questionnaire, clinical examination, and skin prick tests to common allergens. RESULTS: There was no difference in eczema incidence between the probiotic and placebo groups (35[30%] of 118 infants vs 37[27%] of 137 infants, respectively, absolute difference 2.65%, 95% CI -8.45 to 13.75). Similarly, the incidence of atopic eczema (6[5%] of 118 vs 3[2%] of 137), food allergy (4[3%] of 124 vs 2[1%] of 154), wheeze (39[31%] of 127 vs 45[29%] of 154), and atopic sensitization (14[13%] of 106 vs 13[11%] of 123) were similar between the probiotic and placebo groups. CONCLUSION: This study found no effect of postnatal administration of a probiotic combination on the incidence of allergic diseases or atopic sensitization in the first 2 years of life in children born very preterm. Evidence that probiotics are effective for prevention of allergic disease in premature infants remains lacking; adequately powered randomized controlled trials evaluating probiotic supplementation for allergy prevention in very preterm infants are needed.

8.
Vaccine ; 38(5): 1186-1193, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31767467

RESUMO

INTRODUCTION: Australia has recently implemented major changes in cervical cancer prevention policies including introduction of primary human papillomavirus (HPV) screening starting at age 25, and replacement of the quadrivalent HPV vaccine with the nonavalent vaccine in the national school-based program. We assessed the feasibility and utility of conducting HPV testing in residual clinical specimens submitted for routine Chlamydia trachomatis screening, as a means of tracking HPV vaccine program impact among young sexually active women. METHODS: De-identified residual specimens from women aged 16-24 years submitted for chlamydia testing were collected from three pathology laboratories in Victoria and New South Wales. Limited demographic information, and chlamydia test results were also collected. Patient identifiers were sent directly from the laboratories to the National HPV Vaccination Program Register, to obtain HPV vaccination histories. Samples underwent HPV genotyping using Seegene Anyplex II HPV 28 assay. RESULTS: Between April and July 2018, 362 residual samples were collected, the majority (60.2%) of which were cervical swabs. Demographic data and vaccination histories were received for 357 (98.6%) women (mean age 21.8, SD 2.0). Overall, 65.6% of women were fully vaccinated, 9.8% partially, and 24.7% unvaccinated. The majority (86.0%) resided in a major city, 35.9% were classified in the upper quintile of socioeconomic advantage and chlamydia positivity was 7.8%.The prevalence of quadrivalent vaccine-targeted types (HPV6/11/16/18) was 2.8% (1.5-5.1%) overall with no differences by vaccination status (p = 0.729). The prevalence of additional nonavalent vaccine-targeted types (HPV31/33/45/52/58) was 19.3% (15.6-23.8%). One or more oncogenic HPV types were detected in 46.8% (95% CI 41.6-52.0%) of women. CONCLUSIONS: HPV testing of residual chlamydia specimens provides a simple, feasible method for monitoring circulating genotypes. Applied on a larger scale this method can be utilised to obtain a timely assessment of nonavalent vaccine impact among young women not yet eligible for cervical screening.

9.
J Infect Dis ; 221(3): 454-463, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31544206

RESUMO

BACKGROUND: Gardnerella vaginalis is detected in women with and without bacterial vaginosis (BV). Identification of 4 G. vaginalis clades raised the possibility that pathogenic and commensal clades exist. We investigated the association of behavioral practices and Nugent Score with G. vaginalis clade distribution in women who have sex with women (WSW). METHODS: Longitudinal self-collected vaginal specimens were analyzed using established G. vaginalis species-specific and clade-typing polymerase chain reaction assays. Logistic regression assessed factors associated with detection of G. vaginalis clades, and multinomial regression assessed factors associated with number of clades. RESULTS: Clades 1, 2, and 3 and multiclade communities (<2 clades) were associated with Nugent-BV. Clade 1 (odds ratio [OR], 3.36; 95% confidence interval [CI], 1.65-6.84) and multiclade communities (relative risk ratio [RRR], 9.51; 95% CI, 4.36-20.73) were also associated with Lactobacillus-deficient vaginal microbiota. Clade 4 was neither associated with Nugent-BV nor Lactobacillus-deficient microbiota (OR, 1.49; 95% CI, 0.67-3.33). Specific clades were associated with differing behavioral practices. Clade 1 was associated with increasing number of recent sexual partners and smoking, whereas clade 2 was associated with penile-vaginal sex and sharing of sex toys with female partners. CONCLUSIONS: Our results suggest that G. vaginalis clades have varying levels of pathogenicity in WSW, with acquisition occurring through sexual activity. These findings suggest that partner treatment may be an appropriate strategy to improve BV cure.

10.
Vaccines (Basel) ; 7(4)2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31795211

RESUMO

The duration of cross-neutralising antibody responses (cross-NAb) following HPV immunisation is unknown. We compared cross-NAb responses in cohort of girls who were either unimmunised or had received immunisation with one, two or three doses of 4vHPV (Gardasil®,Merck Inc.) six years earlier, before and one month after a booster dose of 2vHPV (Cervarix®, GSK). NAb to potentially cross-reactive HPV genotypes 31, 33, 45, 52 and 58 were measured using a HPV pseudovirion-based neutralisation assay. Girls who had previously received at least one dose of 4vHPV had significantly higher NAb titres for HPV31 when compared with unimmunised girls, whereas no difference in NAb titre was observed for four other genotypes (33, 45, 52 and 58). Following a single further immunisation with 2vHPV, NAb titres to each of the five tested HPV genotypes were comparable for girls who previously received one, two or three doses of 4vHPV, and were significantly higher than for previously unimmunised girls. Immunisation with one, two or three doses of 4vHPV induced NAb to HPV31 that persisted for six years, but there was no persistence of NAb to HPV33, 45, 52 or 58. Our results suggest that one or two doses of 4vHPV may provide long-term protection against HPV31.

11.
Sci Rep ; 9(1): 19749, 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31874964

RESUMO

Women-who-have-sex-with-women (WSW) are at increased risk of bacterial vaginosis (BV). We investigated the impact of practices and past BV on the vaginal microbiota within a two-year longitudinal cohort of Australian WSW. Self-collected vaginal swabs were used to characterise the vaginal microbiota using 16S-rRNA gene sequencing. Hierarchical clustering defined community state types (CSTs). Bacterial diversity was calculated using the Shannon diversity index and instability of the vaginal microbiota was assessed by change of CST and Bray-Curtis dissimilarity. Sex with a new partner increased the bacterial diversity (adjusted-coefficient = 0.41, 95%CI: 0.21,0.60, p < 0.001) and instability of the vaginal microbiota, in terms of both change of CST (adjusted-odds-ratio = 2.65, 95%CI: 1.34,5.22, p = 0.005) and increased Bray-Curtis dissimilarity (adjusted-coefficient = 0.21, 95%CI: 0.11,0.31, p < 0.001). Women reporting sex with a new partner were more likely than women reporting no new partner to have a vaginal microbiota characterised by Gardnerella vaginalis (adjusted-relative-risk-ratio[aRRR] = 3.45, 95%CI: 1.42,8.41, p = 0.006) or anaerobic BV-associated bacteria (aRRR = 3.62, 95%CI: 1.43,9.14, p = 0.007) relative to a Lactobacillus crispatus dominated microbiota. Sex with a new partner altered the vaginal microbiota of WSW by increasing the diversity and abundance of BV-associated bacteria. These findings highlight the influence of practices on the development of a non-optimal vaginal microbiota and provide microbiological support for the sexual exchange of bacteria between women.

12.
Expert Rev Vaccines ; 18(11): 1157-1166, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31718338

RESUMO

Introduction: Safety and efficacy of prophylactic HPV vaccines against HPV infection and associated cervical cancers and precursors is well documented in the literature; however, their efficacy against vulval and vaginal endpoints has not been previously assessed.Areas covered: Published results of trials involving licensed HPV vaccines were included. Main efficacy outcomes were histologically confirmed high-grade vulval and vaginal precancer distinguishing those associated with vaccine HPV types and any vulval and vaginal precancerous lesions. Exposure groups included women aged 15-26 or 24-45 years being initially negative for high-risk HPV (hrHPV), negative for the HPV vaccine types, and women unselected by HPV status.Expert opinion: Our results show that the HPV vaccines are equally highly efficacious against vulval/vaginal disease as previously noted for cervical disease. The vaccines demonstrated excellent protection against high-grade vulval and vaginal lesions caused by vaccine-related HPV types among young women who were not initially infected with hrHPV types or types included in the vaccines (vaccine efficacies more than 90%). No protection against high-grade vulval and vaginal lesions associated with HPV16/18 was observed for mid-adult women. Trials were not powered to address protection against invasive cancers.

13.
J Clin Microbiol ; 58(1)2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31694973

RESUMO

The aim of this study was to determine whether Chlamydia trachomatis could be detected in saliva and if infection is specific to an anatomical site in the oropharynx. Men who have sex with men (MSM) who were diagnosed with oropharyngeal chlamydia at the Melbourne Sexual Health Centre in 2017-2018 were invited to participate upon returning for treatment. Swabs at the tonsillar fossae and posterior oropharynx and a saliva sample were collected. Throat samples were tested for C. trachomatis by the Aptima Combo 2 assay. The bacterial loads of C. trachomatis in all samples were assessed by quantitative PCR (qPCR) detecting the ompA gene. We calculated the positivity and bacterial load of C. trachomatis for all samples. Forty-two MSM were included. The median age was 28 years (interquartile range [IQR], 24 to 33 years). Thirty-two participants (76.2%; 95% confidence interval [CI], 60.5% to 87.9%) had C. trachomatis detected by qPCR at both the tonsillar fossae and the posterior oropharynx, followed by 9.5% (n = 4; 95% CI, 2.7% to 22.6%) positive at the posterior oropharynx only and 4.8% (n = 2; 95% CI, 0.58% to 16.2%) positive at the tonsillar fossae only. Twenty-nine MSM had C. trachomatis detected in saliva (69.0%; 95% CI, 52.9% to 82.3%). The median C. trachomatis load in saliva was 446 copies/ml (IQR, 204 to 1,390 copies/ml), that in the tonsillar fossae was 893 copies/swab (IQR, 390 to 13,224 copies/ml), and that in the posterior oropharynx was 1,204 copies/swab (IQR, 330 to 16,211). There was no significant difference in C. trachomatis load between the tonsillar fossae and the posterior oropharynx (P = 0.119). Among MSM with oropharyngeal chlamydia, nearly three-quarters had chlamydia DNA detected in saliva, although the viability and implications for transmission are unknown.

14.
Vaccine ; 37(43): 6271-6275, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31521414

RESUMO

The Victorian Government introduced a time-limited quadrivalent human papillomavirus (HPV) vaccination catch-up program targeting gay and bisexual men who have sex with men (MSM) aged up to 26 years in 2017. As of 2017, men aged ≥20 years were not eligible for the school-based HPV vaccination program. This study examined the prevalence of anal HPV among 496 MSM aged 20-26 years before they received the first dose of the HPV vaccine at the Melbourne Sexual Health Centre, Australia. More than half (56.5%) had any high-risk HPV genotypes detected in the anus. Almost half (43.1%) had at least one quadrivalent HPV vaccine-preventable genotype (6, 11, 16 or 18) and one-fifth (21.0%) had HPV 16 detected in the anus. These findings suggest that a targeted catch-up HPV vaccination program for MSM is still beneficial to protect against high-risk HPV genotypes associated with anal cancer, as well as low-risk HPV genotypes.

15.
Vaccine ; 37(46): 6907-6914, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31562001

RESUMO

BACKGROUND: Australia introduced a school-based human papillomavirus (HPV) vaccination program for females aged 12-13 years in 2007, with a three-year catch-up to age 26; and for boys aged 12-13 from 2013, with a two-year catch-up to age 15. This study aimed to compare the prevalence of penile HPV between teenage heterosexual males in cohorts eligible or non-eligible for the school-based male vaccination program. METHODS: Between 2014 and 2017, sexually active heterosexual males aged 17-19 were recruited from sexual health centres and community sources across Australia. Males provided a self-collected penile swab for 37 HPV genotypes using Roche Linear Array and completed a questionnaire. We calculated adjusted prevalence ratios (aPR) of HPV between males in two periods: 2014-2015 (preceding implementation of school-based male vaccination) and 2016-2017 (eligible for school-based male vaccination). Self-reported vaccine doses were confirmed with doses reported to the National HPV Vaccination Program Register. RESULTS: Overall, 152 males were recruited in 2014-2015 and 146 in 2016-2017. Numbers of female sex partners and condom use did not differ between the two periods. The prevalence of quadrivalent vaccine-preventable [4vHPV] genotypes (6/11/16/18) was low in both periods (2.6% [2014-15] versus 0.7% [2016-17]; p = 0.371; aPR 0.28 [95% CI: 0.03-2.62]). Compared with men in 2014-2015, men in 2016-2017 had a lower prevalence of any of the 37 HPV genotypes tested (21.7% versus 11.6%; aPR 0.62 [95% CI: 0.36-1.07]) and any of the 13 high-risk genotypes tested (15.8% versus 7.5%; aPR 0.59 [95% CI: 0.30-1.19]). Prevalence of low-risk HPV genotypes did not differ between the two periods. Of the males recruited in 2016-2017, 55% had received ≥1 vaccine dose. CONCLUSION: The prevalence of 4vHPV genotypes among teenage heterosexual males in both cohorts was low, presumably due to herd protection from the female-only vaccination program. Further studies are required to determine the impact of universal HPV vaccination on HPV prevalence in males.

16.
J Clin Microbiol ; 57(11)2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31434719

RESUMO

Mycoplasma genitalium causes a common sexually transmitted infection with a marked propensity to develop antimicrobial resistance. As few treatment options exist, this poses significant challenges to clinicians. Recent diagnostic advances have resulted in tests that report the simultaneous detection of M. genitalium and any resistance to macrolides, the first-line treatment. This allows for therapy to be tailored to the individual, thereby optimizing treatment outcomes. However, resistance to fluoroquinolones, the second-line treatment, is increasing in M. genitalium In this study, we describe a new assay, MG+parC (beta), which simultaneously reports the detection of M. genitalium and five parC mutations that have been associated with resistance to fluoroquinolones. These mutations affect the amino acid sequence of ParC at residues S83R (A247C), S83I (G248T), D87N (G259A), D87Y (G259T), and D87H (G259C). The study tested the MG+parC (beta) assay with 202 M. genitalium-positive clinical samples from Australia (n = 141) and Spain (n = 61). Compared to Sanger sequencing, the assay performed with a kappa value of 0.985 (95% confidence interval [CI], 0.955 to 1.000), with a mutation detection sensitivity of 97.6% (95% CI, 87.4 to 99.9), and specificity of 100.0% (95% CI, 97.7 to 100.0). Fluoroquinolone resistance-associated mutations in parC targeted by the assay were more prevalent among the Australian cohort (23.4% [95% CI,16.3 to 31.8]) compared to the Spanish population (8.8% [95% CI, 2.9% to 19.3%]) (P = 0.019). The MG+parC (beta) kit is a simple and reliable method for simultaneous detection of M. genitalium and fluoroquinolone resistance-associated mutations in clinical settings. This novel diagnostic tool may extend the utility of the second line of antimicrobial therapies in M. genitalium infection.

17.
Infect Drug Resist ; 12: 1951-1967, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308715

RESUMO

Human papillomavirus (HPV) types 16 and 18 cause 70% of cervical cancer cases globally. The nonavalent HPV vaccine (9vHPV) was licensed in 2014 and protects against the next five most common cancer-causing HPV types (HPV 31/33/45/52/58) after HPV 16/18. Phase III clinical studies have demonstrated high vaccine efficacy (>90%) against cervical, vulvar, and vaginal precancers caused by these additional types, and have shown comparable immunogenicity to the shared genotypes to quadrivalent HPV vaccine (4vHPV). Vaccine efficacy and antibody responses for 9vHPV are found to persist for at least five years while longer-term observational studies are ongoing to monitor long-term vaccine effectiveness. The implementation of 9vHPV has the potential to prevent up to 93% of cervical cancer cases, as well as a significant proportion of other HPV-related anogenital cancers. This review article summarizes the current evidence for 9vHPV in terms of vaccine efficacy against HPV infection and related anogenital precancers, safety, and immunogenicity, as well as discussing the potential impact of this vaccine on the cervical cancer burden globally.

18.
Papillomavirus Res ; 8: 100175, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31276802

RESUMO

BACKGROUND: In a 2012 pilot, 9111 Mongolian girls aged 11-17 years received three doses of the quadrivalent (4vHPV) vaccine, Gardasil®. This is the first study to measure early vaccine effectiveness and assess knowledge and attitudes of young women in Mongolia in relation to the human papillomavirus (HPV), the vaccine and cervical cancer. METHODS: A cohort of women vaccinated in 2012 (n = 726) and an unvaccinated cohort (n = 790) provided self-administered vaginal swabs for detection of high-risk HPV genotypes 16, 18/45, 31, 33, 35, 39, 51, 52, 56, 58, 59, 66, 68 five years following vaccination. Participant knowledge and attitudes were assessed through a questionnaire. RESULTS: A total of 1882 questionnaires and 1516 self-administered vaginal swabs were analyzed. The prevalence of any HRHPV was 39.5% among both cohorts. The prevalence of vaccine-targeted HPV types was significantly lower in the vaccinated cohort than unvaccinated: 4.8% and 17.2% respectively. The 4vHPV was shown to be protective against HRHPV 16, 18/45 with 75% vaccine effectiveness. Participant knowledge was low. CONCLUSIONS: This study demonstrates that the 4vHPV is associated with reduced vaccine-targeted HPV detection rates in young Mongolian women. The questionnaire results highlight a need for awareness-raising initiatives in Mongolia on HPV, the vaccine and cervical cancer.

19.
Med J Aust ; 211(3): 113-119, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31168828

RESUMO

OBJECTIVES: To report human papillomavirus (HPV) testing patterns and rates of oncogenic HPV-positivity for specimens submitted during the first 6 months after the National Cervical Screening Program switched from cytology- to primary HPV-based screening. DESIGN, PARTICIPANTS: Retrospective cross-sectional review of 195 606 specimens submitted for HPV testing, 1 December 2017 - 31 May 2018. SETTING: Large community-based general pathology laboratory in metropolitan Sydney. MAIN OUTCOME MEASURES: Prevalence of oncogenic HPV types (all, HPV16/18, non-HPV16/18) by reason for HPV test (primary screening, non-screening); for oncogenic HPV-positive women in the age band recommended for primary HPV screening (25-74 years), prevalence of cytologic abnormality and rates of 12-month follow-up and colposcopy recommendations. RESULTS: 195 606 samples were received: 157 700 (80.6%) for primary screening, 37 906 (19.4%) for non-screening tests. Oncogenic HPV was detected in 8.1% of screening tests (95% CI, 7.9-8.2%) and 20.9% of non-screening tests (95% CI, 20.5-21.3%); 35.5% (95% CI, 34.7-36.4%) of women of recommended screening age with positive oncogenic HPV screening test results also had a cytologic abnormality. The proportion of HPV16/18-positive samples with high grade abnormality was 15.3% (95% CI, 14.2-16.6%); for samples positive for other oncogenic HPV types, the proportion was 6.3% (95% CI, 5.8-6.8%). Repeat HPV testing after 12 months was recommended for 5.4% (95% CI, 5.3-5.5%) and direct colposcopy for 2.6% (95% CI, 2.5-2.7%) of screened women aged 25-74 years. CONCLUSIONS: High grade cytologic abnormalities were more common in women positive for HPV16/18, supporting their higher risk classification. Colposcopy referral rates were higher than during primary cytology-based testing, as predicted by clinical trial and modelling data. The prevalence of HPV was much higher in non-screening than in primary screening samples. Our findings indicate the renewed program is performing as expected during the initial HPV screening round.


Assuntos
Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Programas de Rastreamento/métodos , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Austrália/epidemiologia , Colposcopia , Análise Custo-Benefício , Estudos Transversais , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/prevenção & controle , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal
20.
J Clin Microbiol ; 57(9)2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31243085

RESUMO

Mycoplasma genitalium is a common sexually transmitted infection with a propensity to acquire resistance to commonly used antimicrobial therapies. Bacterial load has been linked to patient symptoms and the success of treatment. In this study, we demonstrate methodology to estimate load from routine diagnostic assays using the ResistancePlus MG test (SpeeDx Pty Ltd., Australia). The method gave comparable quantitation to an M. genitalium-specific 16S rRNA quantitative PCR (qPCR; Spearman r = 0.94) for the samples analyzed (n = 499, including urine and swab types as detailed below) and was, therefore, employed to analyze typical load levels for samples in a diagnostic laboratory (total of 1,012 tests). When stratified by sample type, female urine (median, 826 genomes/ml) had the lowest load. This was significantly lower than median loads for all other sample types (male urine [6.91 × 103 genomes/ml], anal swabs [5.50 × 103], cervical swabs [8.15 × 103], endocervical swabs [3.97 × 103], and vaginal swabs [6.95 × 103]) (P < 0.0001). There were no significant differences in load estimates between the other sample types. Reproducibility of load estimates conducted on the same samples was high (r > 0.85). In conclusion, this methodology to provide load estimates for M. genitalium can be easily integrated into routine diagnostic laboratory workflow. Given the association between organism load, symptoms, and treatment success, load assessment has future diagnostic potential.

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